The major goals of these studies are to elucidate the individual roles of COX-1 and COX-2 in normal physiology and in various pathological states using the COX deficient mice. Included in these studies are the roles of the COX isoforms in gastric ulceration, lung inflammation and vascular development. Our early studies in COX deficient mice was to investigate gastric ulceration, inflammatory responses and kidney development (Cell 83: 473 and 483, 1995). More recent interest in the laboratory has been to study the effects of COX deficiency on lung inflammation and mucus production. Additionally, effort within the laboratory has focused on using COX-1 and COX-2 deficient ES cells to study the roles of the COXs in vascular development. Mice and ES cells deficient in both COX-1 or COX-2 have been produced. Functional COX-2, and not COX-1, is involved in the lungs inflammatory response. Preliminary studies also suggest that both COX-1 and COX-2 have roles in ES cell differentiation into vascular precussor cells. Studies with COX-1 and COX-2 selective inhibitors have been used and are in agreement, and extend, the data obtained with the genetically deficient COX mice and ES cells.